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Nat Commun. 2017 May 23;8:15408. doi: 10.1038/ncomms15408.

Rules of engagement between αvβ6 integrin and foot-and-mouth disease virus.

Author information

1
Division of Structural Biology, The Nuffield Department of Medicine, University of Oxford, The Henry Wellcome Building for Genomic Medicine, Headington, Oxford OX3 7BN, UK.
2
National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing 100101, China.
3
Program in Cellular and Molecular Medicine and Division of Hematology, Department of Medicine, Boston Children's Hospital, Boston, Massachusetts 02115, USA.
4
Department of Biological Chemistry &Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
5
Structural Biology Unit, CIC bioGUNE, CIBERehd, 48160 Derio, Spain.
6
Laboratory of Structural Biology, School of Medicine, Tsinghua University, Beijing 100084, China.
7
Pirbright Institute, Pirbright GU24 0NF, UK.
8
IKERBASQUE, Basque Foundation for Science, 48013 Bilbao, Spain.
9
Diamond Light Sources, Harwell Science and Innovation Campus, Didcot OX11 0DE, UK.

Abstract

Foot-and-mouth disease virus (FMDV) mediates cell entry by attachment to an integrin receptor, generally αvβ6, via a conserved arginine-glycine-aspartic acid (RGD) motif in the exposed, antigenic, GH loop of capsid protein VP1. Infection can also occur in tissue culture adapted virus in the absence of integrin via acquired basic mutations interacting with heparin sulphate (HS); this virus is attenuated in natural infections. HS interaction has been visualized at a conserved site in two serotypes suggesting a propensity for sulfated-sugar binding. Here we determined the interaction between αvβ6 and two tissue culture adapted FMDV strains by cryo-electron microscopy. In the preferred mode of engagement, the fully open form of the integrin, hitherto unseen at high resolution, attaches to an extended GH loop via interactions with the RGD motif plus downstream hydrophobic residues. In addition, an N-linked sugar of the integrin attaches to the previously identified HS binding site, suggesting a functional role.

PMID:
28534487
PMCID:
PMC5457520
DOI:
10.1038/ncomms15408
[Indexed for MEDLINE]
Free PMC Article

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